Connecting Spleen Volume Reduction to Survival Outcomes in MF


During a Case-Based Roundtable® event, Raajit K. Rampal, MD, PhD, discussed the correlation between spleen volume responses and survival outcomes for patients with myelofibrosis in the second article of a 2-part series.


A 68-year-old woman presented to her physician with symptoms of mild fatigue. Her spleen was palpable 6-7 cm below the left costal margin​, but she had no known comorbidities. Next-generation sequencing revealed a JAK2 V617F mutation​, and her karyotype was46XX.​ A bone marrow biopsy showed megakaryocyte proliferation and atypia with evidence of reticulin fibrosis​, and a blood smear was positive for leukoerythroblastosis​.

Her laboratory values also led to a diagnosis of primary myelofibrosis (MF). Risk stratification based on the dynamic international prognostic scoring system gave her a score of intermediate-1, and based on the mutation-enhanced international prognostic score system for transplantation-age she was also determined to be at intermediate risk​.


  • Did the overall survival data from the COMFORT-I trial (NCT00952289) and COMFORT-II trial (NCT00934544) impact the way you manage patients with MF?​
  • How do you monitor and manage anemia in patients with primary MF prior to starting Janus kinase (JAK) inhibitor therapy?​

RAAJIT K. RAMPAL, MD, PHD: If you look at several pieces of data, there is a correlation between [the patient] achieving a spleen volume reduction [SVR] and overall survival [OS] results. This a key finding [when looking] at pooled data from COMFORT-I and COMFORT-II and the RUXOREL-MF study [NCT03959371], which used the response to ruxolitinib after 6 months [RR6] model that looked at factors associated with survival and patients treated [with ruxolitinib (Jakafi)] in the real world.1,2 Both of those analyses demonstrated that achieving at least a 35% spleen volume response correlated to better survival.

Raajit K. Rampal, MD, PhD​Director, Center for Hematologic Malignancies

Director, Myeloproliferative Neoplasms Program

Memorial Sloan Kettering Cancer Center​

New York, NY

Raajit K. Rampal, MD, PhD​Director, Center for Hematologic Malignancies

Director, Myeloproliferative Neoplasms Program

Memorial Sloan Kettering Cancer Center​

New York, NY

Now, does it have to be at least a 35% reduction? No, in fact, if you look at the pooled COMFORT-I and COMFORT-II data, as much as a 10% SVR does increase odds of survival.1 There is a trend towards increasing survival benefit as the amount of SVR increases, but it's not statistically significant.1 However, I think that does argue that achieving a SVR is an important thing.

SUBHASH C. PROOTHI, MD: If we are making patients more anemic with this therapy, are we not affecting their quality of life?

RAMPAL: In somebody who has a preserved hemoglobin, in the first 3 months you may expect there is going to be a decrease in hemoglobin and you're going to potentially have to transfuse them or give an [erythropoiesis stimulating agent], but it will recover to a reasonable number after 3 months.

Longer term it becomes more problematic; in other words, there is this RR6-model that demonstrated if the patient continues to be transfusion dependent by about 6 months, there is a detrimental effect on survival.2 But to your point, of course that's going to also have a detrimental effect on the patient's quality of life if you're committing them to transfusions.

ALEXANDER BARSOUK, MD: We see this OS difference [with these data]. But my question is, for those patients who were randomly assigned, when did their treatment start? [Did it start] when they were diagnosed or when they developed symptoms?

RAMPAL: In order to qualify for the COMFORT trials, the patient had to have a certain symptom burden measured by the total symptom score. Some of these patients were recently diagnosed patients, however, they had to have a certain threshold of spleen and symptoms to qualify for the study. So, does that apply to the patients that we see in the real world? Not entirely.


1. Vannucchi AM, Kantarjian HM, Kiladjian JJ, et al; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015 Sep;100(9):1139-45. doi:10.3324/haematol.2014.119545

2. Maffioli M, Mora B, Ball S, et al. A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis. Blood Adv. 2022;6(6):1855-1864. doi:10.1182/bloodadvances.2021006889

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